Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys

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Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Associa:on of phthalates, parabens and phenols in
   personal care products with pubertal :ming
                 in girls and boys
                             v
                      Kim Harley, PhD
              University of California, Berkeley

         Collabora:ve on Health and the Environment
                Genera:on Chemical Webinar
                        Jan 28, 2021
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Personal Care Products: What’s the Concern?
                  • The average woman uses 12 personal care products a day
                  • The average teenage girl uses 17
                  • More than 12,500 chemicals are used in cosme:cs and personal care products

          Cosme:cs                     Fragrance

                                                                                         Lo:on

                                      Soap & Shampoo   Deodorant
                                                                                Toothpaste

                                                           Sunscreen

Source: Environmental Working Group
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
These Chemicals Can Enter our Bodies

                         Inhala:on

Inges:on
                                         Dermal Absorp:on
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Suspected Endocrine Disruptors in
                    Personal Care Products
Phthalates
• Diethyl phthalate (DEP)
• Di-n-butyl phthalate (DBP)                     Parabens
• Di-isobutyl phthalate (DiBP)                   • Methyl Paraben (MP)
                                                 • Propyl Paraben (PP)

     An:bacterials
     • Triclosan (TCS)
                                 Sunscreens
                                 • Benzophenone-3 (BP-3)
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Personal Care Products are the Main
                                                               Source of Exposure
                                                    Urinary BP-3                                                                     Urinary Propyl Paraben
                                              500                                                              50

                                                                       Geometric Mean Propyl Paraben (ng/ml)
                                                      P-value < 0.01                                                P-value < 0.01           P-value = 0.05
          Geometric Mean BP3 Levels (ng/ml)

                                                                                                                                                               P-value < 0.01
                                              400                                                              40

                                              300                                                              30

                                              200                                                              20

                                              100
                                                                                                               10

                                                0
                                                                                                               0
                                                      No    Yes
                                                                                                                         No    Yes          No    Yes           No    Yes
                                                     Used Sunscreen                                                    FoundaIon              Blush              Mascara
                                                     Past 24 hours?                                                   Past 24 hours?      Past 24 hours?      Past 24 hours?
Berger et al, 2018
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Timing of Puberty in Girls is Ge_ng Earlier
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Evidence Suggests this is a Global Phenomenon

           Age of First Breast Development

                                                         Age at onset of breast
                      p-value = 0.02
                                                       development has decreased
                                                        by one year over past 40
                                                                 years

                                             Eckert-Lind et al, JAMA Pediatrics, 2020
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
How Do We Measure Pubertal Timing?
                                        Girls:
                                        • Breast development (thelarche)
                                        • Pubic hair development (pubarche)
                                        • Menarche

                                        Boys:
                                        • Tes:cular volume >3 ml
                                        • Genital development
                                        • Pubic hair development

                                      Trend towards earlier puberty in girls is quite well-established.
                                      Trend in boys is less clear.
Edvard Munch, Na:onal Gallery, Oslo
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Associa:ons with Puberty: Animal Studies

      • LMW phthalates:
         • Earlier puberty in female rats
         • Later puberty in male rats

      • Parabens:
         • Earlier puberty in female rats
         • Later puberty in male rats
                                                                                      Mean age of onset of vaginal opening following an oral exposure

      • Triclosan:                                                                    to triclosan from PND 21 to 42 in the female pubertal assay
                                                                                      (From: Stoker et al, Tox Sci, 2010)

         • Earlier puberty in female rats

Hu 2013, Sallenfait 2008, Vo 2010, Kang 2001, Zhang 2014, Stoker 2012, Zorilla 2009
Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
Research Ques:on

Is :ming of puberty in children associated with personal care product
chemical exposure at two cri:cal :me points:
 • In utero (biomarkers in maternal urine during pregnancy)
 • Pre-puberty (biomarkers child urine at age 9)
CHAMACOS
                                Longitudinal Birth Cohort
                                                    N = 338 Study

          Birth          1 yr          3 ½ yr          7 yr          10 ½ yr         14 yr           18 yr
                                                                          11 ¼
       N = 538                                                       N = 338
                                                                     9¾            12 ¾
Pregnancy         6 mo          2 yr            5 yr          9 yr             12 yr         16 yr
(two visits)
Findings:
Associa:ons with Timing of Puberty
Associa:on of Prenatal Urinary Metabolites (con:nuous)
                         and Puberty in Girls
                                            Breast Development                                                                                Pubic Hair Development
                                3                                                                                               3
           Mean Shio (months)

                                2                                                                                               2

                                                                                                           Mean Shio (months)
                                1                                                                                               1
                                0                                                                                               0
                                -1                                                                                              -1
                                -2                                                                                              -2
                                -3                                                                                              -3
                                     MEP   MBP   MiBP     TCS                     BP3   MP    PP                                       MEP    MBP        MiBP   TCS   BP3    MP     PP

                                                                                              Menarche
                                                                             3                                                                                  Adjus:ng for:
                                                                                                                                                                • Family income
                                                        Mean Shio (months)

                                                                             2
                                                                             1                                                                                  • Mother’s educa:on
                                                                             0
                                                                                                                                                                • Mother’s years of residence in US
                                                                                                                                                                • Mother’s pre-pregnancy BMI
                                                                             -1
                                                                             -2
                                                                             -3
Harley et al, Human Repro, 2019                                                   MEP   MBP   MiBP   TCS                         BP3     MP         PP
Quar:les of Prenatal MEP and Puberty in Girls

                                                       Prenatal MEP and thelarche                              Prenatal MEP and pubarche
                                                 10                                                      10

                                                  5                                                       5
                            Mean Shio (months)

                                                                                    Mean Shio (months)
   MEP = metabolite of                            0                                                       0
   diethyl phthalate
                                                  -5                                                      -5
                                                                                                                                           Adjus:ng for:
                                                 -10                                                     -10                               •   Family income
                                                                                                                                           •   Mother’s educa:on
                                                                                                                                           •   Mother’s years of
                                                                                                                                               residence in US
                                                 -15                                                     -15                               •   Mother’s pre-
                                                         Q1    Q2   Q3     Q4                                    Q1    Q2   Q3    Q4           pregnancy BMI
                                                       (Ref)                                                   (Ref)

    • Highest quar:le of prenatal MEP associated with 5-6 months earlier pubertal onset
Harley et al, Human Repro, 2019
Quar:les of Prenatal Triclosan and Menarche in Girls

                                                              Prenatal Triclosan and menarche
                                                        10

                                                         5

                                   Mean Shio (months)
                                                         0
      Triclosan =
      An:bacterial agent                                 -5
                                                                                                Adjus:ng for:
                                                                                                •   Family income
                                                        -10                                     •   Mother’s educa:on
                                                                                                •   Mother’s years of
                                                                                                    residence in US
                                                        -15                                     •   Mother’s pre-
                                                                   Q1    Q2      Q3     Q4          pregnancy BMI

                                                                (Ref)

      • Highest quar:le of prenatal Triclosan associated with 4 months earlier menarche
Harley et al, Human Repro, 2019
Associa:on of Childhood (age 9) Urinary Metabolites
                   (con:nuous) and Puberty in Girls
                                                      Breast Development                                                                                                     Pubic Hair Development
                               3                                                                                                                           3

                               2                                                                                                                           2
          Mean ShiP (months)

                                                                                                                                      Mean ShiP (months)
                               1                                                                                                                           1

                               0                                                                                                                           0
                                          Phthalates not                                                                                                         Phthalates not
                               -1                                                                                                                          -1
                                            measured                                                                                                               measured
                               -2                                                                                                                          -2

                               -3                                                                                                                          -3
                                    MEP        MiBP        MnBP                        TCS     BP3         MP         PP                                        MEP      MiBP     MnBP   TCS     BP3   MP    PP

                                                                                                                           Menarche
                                                                                       3                                                                                                 Adjus:ng for:
                                                                                       2                                                                                                 • Family income
                                                                  Mean ShiP (months)

                                                                                       1                                                                                                 • Mother’s educa:on
                                                                                       0
                                                                                                                                                                                         • Mother’s years of residence in US
                                                                                                   Phthalates not
                                                                                                                                                                                         • Mother’s pre-pregnancy BMI
                                                                                       -1
                                                                                                     measured
                                                                                       -2
                                                                                       -3
                                                                                             MEP        MiBP        MnBP      TCS                BP3             MP        PP
Harley et al, Human Repro, 2019
Quar:les of Childhood (age 9) Methyl Paraben and
                 Pubertal Milestones in Girls
Methyl paraben =
preserva:ve
                                     Childhood MP and thelarche                              Childhood MP and pubarche                              Childhood MP and menarche
                               10                                                      10                                                     10

                                5                                                       5                                                      5
          Mean Shio (months)

                                                                                                                         Mean Shio (months)
                                                                  Mean Shio (months)
                                0                                                       0                                                      0

                                -5                                                      -5                                                     -5

                               -10                                                     -10                                                    -10

                               -15                                                     -15                                                    -15
                                        Q1    Q2     Q3     Q4                                 Q1     Q2     Q3     Q4                                 Q1     Q2    Q3    Q4
                                      (Ref)                                                   (Ref)                                                   (Ref)

                               • Highest quar:le of childhood methyl paraben concentra:ons associated
                                 with 6 months earlier pubarche and menarche
Associa:on of Urinary Metabolites (con:nuous) and
                               Puberty in Boys
                                                Genital Development                                                     Pubic Hair Development
  Prenatal                          4                                                                         4
              Mean Shio (Months)

                                                                                        Mean Shio (Months)
  Exposure
                                    2                                                                         2

                                    0                                                                         0

                                   -2                                                                        -2

                                   -4                                                                        -4
                                        MEP     MBP        MiBP   TCS   BP3   MP   PP                             MEP      MBP      MiBP   TCS   BP3   MP   PP

                                                Genital Development                                                          Pubic Hair Development
 Childhood                         4                                                                         4
              Mean Shio (Months)

 Exposure

                                                                                        Mean Shio (Months)
                                   2      Phthalates not                                                     2
                                                                                                                    Adjus:ng for:
                                                                                                                   Phthalates not
 (9 years)                                  measured                                                                • Family income
                                                                                                                     measured
                                   0                                                                         0      • Mother’s educa:on
                                   -2                                                                        -2     • Mother’s years of residence in US
                                   -4                                                                               • Mother’s pre-pregnancy BMI
                                                                                                             -4
                                        MEP     MBP        MiBP   TCS   BP3   MP   PP                             MEP     MBP       MiBP   TCS   BP3   MP   PP

Harley et al, Human Repro, 2019
In Summary…

• Several chemicals in personal care products were associated with earlier puberty in
  girls … but not boys

• Associa:ons with both prenatal and peripubertal exposures

   Prenatal:
   • Highest maternal exposure to diethyl phthalate à 6 months earlier pubarche
   • Highest maternal exposure to triclosan à 4 months earlier menarche

   Peripubertal:
   • Highest childhood exposure to methyl and propyl parabens à 6 months earlier
Reasons for Cau:on

• First study to examine prenatal exposures to some of these
  personal care product chemicals
• Very specific popula:on (low-income, rural La:nas in California)
• Urinary biomarkers reflect short-term exposures (24-48 hours)
• Associa:ons with childhood exposures might reflect reverse
  causa:on.
Policy Implica:ons

• We know that the chemicals in personal care products are ge_ng
  into our bodies.
• Evidence that endocrine disrup:ng chemicals may be impac:ng
  pubertal :ming
• The FDA has very limited authority over the cosme:cs and
  personal care products industry
• Regula:on of cosme:cs is slowing star:ng to change (e.g.
  California Toxic-Free Cosme:cs Act)
Switching your Products can Reduce Exposure!
                  •   Enrolled 100 teen girls
                  •   Collected pre-interven:on urine sample
                  •   Stop using regular personal care products for 3
                      days. Low chemical products instead.
                  •   Collected post-interven:on urine sample
Chemicals in the body decreased in 3 days

                                                   28%         35%                        36%   44%
    SG-Corrected Urinary Concentra1on (ng/ml)

Harley et al, EHP, 2016                                              All p-values
Thanks to:
                                                     Our Research Team
   Our Funders
                                                    UC Berkeley
                                                    Brenda Eskenazi
                                                    Kimberly P. Berger
                                                    Katherine Kogut
Grants: R21 ES024909, P01 ES009605, R01 ES017054,   Kimberly Parra
RC2 ES018792, R01 ES021369, R24 ES028529
                                                    UC San Francisco
                                                    Robert H. Lus:g
      Grants: R82670901, RD83171001,
      RD83451301                                    Kaiser Permanente
                                                    Louise C. Greenspan

                          Grant: 18BB-1800
                                                    Center for Disease Control and Preven:on
                                                    Antonia M. Calafat, Xiaoyun Ye
And a very special
thanks to the
CHAMACOS families!

                     CHAMACOS Study Photo
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